Radiofluorinated Pyrimidine‐2,4,6‐triones as Molecular Probes for Noninvasive MMP‐Targeted Imaging

Matrix metalloproteinases (MMPs) are zinc‐ and calcium‐dependent endopeptidases. Representing a subfamily of the metzincin superfamily, MMPs are involved in the proteolytic degradation of components of the extracellular matrix. Unregulated MMP expression, MMP dysregulation and locally increased MMP activity are common features of various diseases, such as cancer, atherosclerosis, stroke, arthritis, and others. Therefore, activated MMPs are suitable biological targets for the specific visualization of such pathologies, in particular by using radiolabeled MMP inhibitors (MMPIs). The aim of this work was to develop a radiofluorinated molecular probe for noninvasive in vivo imaging for the detection of up‐regulated levels of activated MMPs in the living organism. Fluorinated MMPIs ( 26 , 31 and 38 ) based on the pyrimidine‐2,4,6‐trione lead structure RO 28‐2653 ( 1 ) were synthesized, and their MMP inhibition potency was evaluated in vitro. The radiosynthesis and the in vivo biodistribution of the first ¹⁸F‐labeled prototype, MMP‐targeted tracer [¹⁸F] 26 , suitable for molecular imaging by means of positron emission tomography (PET) were realized.     

A comparison among 1-, 3-, and 7-horn feeds for a 37-beam MBA

A very common multiple beam antenna (MBA) configuration consists of a collimating device illuminated by an array of feeds. The collimating device is usually a reflector or a lens. The feeds are usually horn antennas with a circular aperture. The reflector is usually offset-fed to eliminate aperture blockage; the lens is center fed. The antenna's feeds are excited to produce a finite number of beams, so as to provide contiguous coverage of the field of view. The designer is forced to minimize the angular spacing between adjacent beams in order to maximize the minimum gain over the antenna's field of view. On the other hand, the feed horn's aperture gain is maximized when the feed horn spacing and its aperture diameter are equal. This results in antenna efficiency of the order of 30% when a single feed horn is excited to produce a beam. When a cluster of 3 or 7 adjacent feed horns are excited to produce a single beam, antenna efficiency can be increased to 50%. When it is tolerable, several identical antenna apertures can be used to replace a single aperture configuration. In this case, each of M apertures produces approximately N/M beams of an MBA that produces N beams. Horns producing adjacent beams do not illuminate the same aperture. This permits the use of a much larger horn aperture for a given beam spacing. This results in reduced spillover, higher gain of each beam, and increased antenna efficiency of each aperture. This paper investigates the maximization of gain for several lens antennas. It shows that antenna gain is increased as its focal length is decreased. That is, a focal length-to-diameter ratio (F/D) less than 1 is preferred     

Anthropogenic tracers, endocrine disrupting chemicals, and endocrine disruption in Minnesota lakes

Concentrations of endocrine disrupting chemicals and endocrine disruption in fish were determined in 11 lakes across Minnesota that represent a range of trophic conditions and land uses (urban, agricultural, residential, and forested) and in which wastewater treatment plant discharges were absent. Water, sediment, and passive polar organic integrative samplers (POCIS) were analyzed for steroidal hormones, alkylphenols, bisphenol A, and other organic and inorganic molecular tracers to evaluate potential non-point source inputs into the lakes. Resident fish from the lakes were collected, and caged male fathead minnows were deployed to evaluate endocrine disruption, as indicated by the biological endpoints of plasma vitellogenin and gonadal histology. Endocrine disrupting chemicals, including bisphenol A, 17β-estradiol, estrone, and 4-nonylphenol were detected in 90% of the lakes at part per trillion concentrations. Endocrine disruption was observed in caged fathead minnows and resident fish in 90% of the lakes. The widespread but variable occurrence of anthropogenic chemicals in the lakes and endocrine disruption in fish indicates that potential sources are diverse, not limited to wastewater treatment plant discharges, and not entirely predictable based on trophic status and land use.     

Kinetic masks: a new approach and device for dispersing biologically relevant fluids

The controlled dispersion of fluids, particularly biologically relevant solutions in micro-volumes, is of high practical interest in biotechnology and medicine. Pharmaceutical test assays, for example, need a method for the fast and defined deposition of fluid samples. Most current micro-dispensing methods, i.e. contact-based pin printing, have problems such as time delays, limited dosing velocity, minimum volume or high interference that limit biological applications. Spraying techniques suffer from a lack of reproducibility; a defined deposition of samples on targets is not possible. Here, we introduce a new method for the parallel and spatially defined dispersion of many micro-volumes that overcomes disadvantages of common micro-dispensers. The overall approach is that a fluid drop, produced by a droplet generator, falls on a free trajectory with a defined kinetic energy, and is split by a masking unit placed perpendicular to the flight direction into at least two smaller droplets (Zimmermann et al. in Method and device for dosing fluid media, WO/2002/102515, Germany, 2002). On the target, the resulting droplets form reproducible patterns, which are enlarged and scalable images of the grid pattern. Possible applications for this method are non-contact cell patterning, cell encapsulation, cryopreservation and fast mixing processes in micro-volumes. Here, we use this method for the direct and defined parallel positioning of cell suspensions on specific substrates, which can be useful for test assays, tissue engineering and cryopreservation.     

Several ways to produce porous carbon monoliths by template assisted routes

Several ways to produce microporous and mesoporous carbon monoliths by template assisted synthesis routes are described. Pressed zeolite (HY) and silica powder tablets have been used as templates. Sucrose acts as a carbon precursor and as a binder between the carbon particles as well. In the case of zeolite template, the carbon porosity could be increased by additional loading of the template with ethene. Due to the balance between mechanic stability and porosity of the carbon monolith, an optimal amount of sucrose is required. The final products were characterized by low temperature nitrogen adsorption.